Mechanisms of normal and abnormal biochemical differentiation in postembryonic mammalian tissues are the broad subjects of these investigations. Much of the research is concentrated on defining changes in enzyme profile that occur in host tissues, i.e. in liver, spleen, lung and blood of tumor-bearing rats. To determine the extent to which these changes depend on the kind of tumor that caused them, we shall compare rats bearing mammary gland, lymphoid tissue, hepatic and renal tumors. By implanting these into one rat of a parabiont pair and comparing the enzymic abnormalities in both partners, we shall gain further understanding about the systemic mediation of the effect of cancer on the host. Further studies of the mechanism of the host response will involve investigations of enzymic changes in normal rats evoked by the administration of cell free tumor extracts. Cancer studies in man will be restricted to comparison of the concentration of some enzymes (involved in collagen, nucleic acid and non-essential amino acid synthesis) in surgical biopsy samples of lung tumors and non-neoplastic pulmonary areas. Continuation of our studies of tissue differentiation during early postnatal life will center on brain of normal rats as compared to those with experimental hyperphenylalaninemia. BIBLIOGRAPHIC REFERENCES: DelValle, J.A. and Greengard, O.: The regulation of phenylalanine hydroxylase in rat tissues in vivo. I. The maintenance of high plasma phenylalanine concentrations in suckling rats; a model for phenylketonuria. Biochem. J. 154, 613-618, 1976. Greengard, O. and DelValle, J.A.: The regulation of phenylalanine hydroxylase in rat tissues in vivo. II. Substrate and cortisol induced elevations in phenylalanine hydroxylase activity. Biochem. J. 154, 619-624, 1976.